title: Pharmacology at work for cardio-oncology: ranolazine to treat early cardiotoxicity induced by antitumor drugs.
abstract: Antitumor drugs may cause asymptomatic diastolic dysfunction that introduces a lifetime risk of heart failure or myocardial infarction. Cardio-oncology is the discipline committed to the cardiac surveillance and management of cancer patients and survivors; however, cardio-oncology teams do not always attempt to treat early diastolic dysfunction. Common cardiovascular drugs, such as β blockers or angiotensin-converting enzyme inhibitors or others, would be of uncertain efficacy in diastolic dysfunction. This perspective describes the potential value of ranolazine, an antianginal drug that improves myocardial perfusion by relieving diastolic wall tension and dysfunction. Ranolazine acts by inhibiting the late inward sodium current, and pharmacological reasonings anticipate that antitumor anthracyclines and nonanthracycline chemotherapeutics might well induce anomalous activation of this current. These notions formed the rationale for a clinical study of the efficacy and safety of ranolazine in cancer patients. This study was not designed to demonstrate that ranolazine reduced the lifetime risk of cardiac events; it was designed as a short term proof-of-concept study that probed the following hypotheses: 1) asymptomatic diastolic dysfunction could be detected a few days after patients completed antitumor therapy, and 2) ranolazine was active and safe in relieving echocardiographic and/or biohumoral indices of diastolic dysfunction, measured at 5 weeks or 6 months of ranolazine administration. These facts illustrate the translational value of pharmacology, which goes from identifying therapeutic opportunities to validating hypotheses in clinical settings. Pharmacology is a key to the success of cardio-oncology.
authors.affiliation: CIR and Drug Sciences, University Campus Bio-Medico, Rome, Italy. g.minotti@unicampus.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Minotti
mesh_terms: D000083:Acetanilides / Q000494:pharmacology / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D054144:Heart Failure, Diastolic / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000069458:Ranolazine; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000083:Acetanilides; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010879:Piperazines; D000069458:Ranolazine